Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN)

As for all mature B-cell neoplasms, the methods of cytomorphology and histology guide downstream diagnosis.

In SBLPN, the percentage of atypical lymphoid cells in peripheral blood ranges from 20% to 95%. The cells are medium to large in size with abundant basophilic or pale cytoplasm with fine or poorly defined projections. A large, prominent single nucleolus is typically present. The cells are smaller than those of HZL, but occasionally large cells with a binucleate nucleus can be identified. Unlike HZL, the cells do not have circumferential villous processes (WHO 2022).

The bone marrow has normal or increased cellularity, with a variable, often mild degree of lymphocytic infiltration and mild fibrosis. In later stages of disease, a diffuse pattern may occur. The diagnostic feature is considered to be medium-sized atypical lymphoid cells with relatively abundant cytoplasm, round nucleus, and a conspicuous nucleolus (WHO 2022).

The neoplastic cells express monotypic surface immunoglobulin (more commonly IgG, either alone or with another isotype), pan-B cell antigens (CD19, CD20 and CD22, DBA-44), CD11c, CD103 and FMC7. In contrast to classic hairy cell leukemia, CD25, annexin A1, TRAP, and CD123 are not expressed.

Chromosomal analysis is not obligatory in the diagnosis of SBLPN. Due to the low in vitro proliferation of SBLPN cells, there are also few data on cytogenetic alterations so far.

Numerical and structural chromosomal alterations known to date include complex karyotypes involving 14q32, 8q24, 17p deletions, 7q deletions, and trisomy 12 (WHO 2022). Rearrangements involving immunoglobulin loci are also observed in some cases (Brito-Babapulle et al. 1994, Matutes et al. 2001, Angelova et al. 2018).

Like chromosomal analysis, this investigation is not obligatory for the diagnosis of SBLPN. By using different techniques to analyze copy number alterations, 17p deletions (TP53) as well as 11q deletions (ATM) could be described especially for SBLPN (Dierlamm et al. 2001, Hockley et al. 2011), these can also be detected by FISH (Matutes et al. 2001, Angelova et al. 2018).

In contrast to HZL, SBLPN do not show mutation of BRAF V600E. The immunoglobulin gene repertoire shows a shift to preferential occurrence of the IGHV4-34 gene, mostly with a small number of somatic hypermutations. Characteristic of SBLPN cases is the association with MAP2K1 mutations in almost 50% of cases (WHO 2022).

Overall, molecular genetic features suggest that SBLPN are more closely related to splenic marginal zone lymphoma (SMZL) or splenic diffuse red pulp small B-cell lymphoma (SDRPL) than to HZL. However, as the definition is constantly evolving, these aspects need to be revisited (WHO 2022).